The purpose of this project is to delineate the mechanisms involved in regulating immune responses in filarial and nonfilarial disease states. Immunoregulatory studies have examined the phenomenon of antigen-specific anergy in microfilaremic patients by showing this anergy to be a result of the production of the antiproliferative cytokine, IL-10, made by both monocytes and CD4+ cells (of the Th2 type). The phenotypic characterization of these Th2 CD4+ cells has shown them to be CD45RO+CD27-; a novel method for intracellular staining for cytokines has shown that IL-5 and interferon gamma are the best discriminators of Th2 and Th1 T-cell subsets. Using selected recombinant filarial antigens, the role the antigens themselves play in the induction of a Th2 response and the B cell response it subsequently influences (IgE/IgG4) has been studied. Similarly, new ways of assessing eosinophil activation have also been developed. Clinical epidemiological and parasitological assessment of individuals who are "putatively immune" to either onchocerciasis or lymphatic filariasis have been identified. These individuals very clearly mount augmented cellular responses to parasite antigens and, for those immune to onchocerciasis, responses to a recombinant antigen (OV20/11) have been associated with resistance, and suggests a mechanism for protection. The genetics underlying susceptibility and resistance to filarial infection has been studied by HLA Class II typing along with allotyping. A particular KM allotype has been identified as correlating with resistance to infection. Also, a number of novel DQ and DP alleles have been identified.